180,397 results on '"Lea, A"'
Search Results
2. 6 Hidden in the Code
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Lea, Andrew S.
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- 2023
3. Part III: Physician
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Lea, Andrew S.
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- 2023
4. 5 MYCIN Explains Itself
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Lea, Andrew S.
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- 2023
5. 1 Indexing the World
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Lea, Andrew S.
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- 2023
6. Index
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Lea, Andrew S.
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- 2023
7. Conclusion
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Lea, Andrew S.
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- 2023
8. 4 The Medical Mind
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Lea, Andrew S.
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- 2023
9. 3 The Disease Concept Incarnate
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Lea, Andrew S.
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- 2023
10. 2 The Statistical Patient
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Lea, Andrew S.
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- 2023
11. Half Title Page
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Lea, Andrew S.
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- 2023
12. Part II: Disease
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Lea, Andrew S.
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- 2023
13. Acknowledgments
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Lea, Andrew S.
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- 2023
14. Half Title Page, Series Information, Title Page, Copyright, Dedication
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Lea, Andrew S.
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- 2023
15. The Mirror and the Mind: A History of Self-Recognition in the Human Sciences by Katja Guenther (review)
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Lea, Andrew S.
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- 2023
- Full Text
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16. The Professional Well-Being of Early Educators in California. Early Educator Well-Being Series
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University of California, Berkeley. Center for the Study of Child Care Employment (CSCCE), Wanzi Muruvi, Anna Powell, Yoonjeon Kim, Abby Copeman Petig, and Lea J. E. Austin
- Abstract
Our look at the well-being of California's early educators points to the need to consider work environments in early care and education (ECE) policy development. The learning environments of young children are also the work environments of the ECE workforce. Supportive and safe work environments that foster a respectful workplace climate can enhance educators' practice, professional esteem, and job satisfaction. This is the second of three reports, drawn from our statewide survey of nearly 1,800 early educators. Our findings show that: (1) Though the majority of early educators find satisfaction and reward from their work with children, many feel their work is not respected; (2) Despite their dedication to their profession, many educators encounter inadequate work environments: more than two thirds of center teachers are given duties no one else wants, and nearly a tenth have been the target of racial slurs at work; and (3) Working with children with challenging behaviors, finding planning time and spending time with individual children are common classroom challenges.
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- 2024
17. Characterization of more than three years of in-orbit radiation damage of SiPMs on GRBAlpha and VZLUSAT-2 CubeSats
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Ripa, Jakub, Dafcikova, Marianna, Kosik, Pavel, Münz, Filip, Ohno, Masanori, Galgoczi, Gabor, Werner, Norbert, Pal, Andras, Meszaros, Laszlo, Csak, Balazs, Fukazawa, Yasushi, Takahashi, Hiromitsu, Mizuno, Tsunefumi, Nakazawa, Kazuhiro, Odaka, Hirokazu, Ichinohe, Yuto, Kapus, Jakub, Hudec, Jan, Frajt, Marcel, Rezenov, Maksim, Daniel, Vladimir, Svoboda, Petr, Dudas, Juraj, Sabol, Martin, Laszlo, Robert, Koleda, Martin, Duriskova, Michaela, Szakszonova, Lea, Kolar, Martin, Husarikova, Nikola, Breuer, Jean-Paul, Hroch, Filip, Vitek, Tomas, Vertat, Ivo, Urbanec, Tomas, Povalac, Ales, Kasal, Miroslav, Hanak, Peter, smelko, Miroslav, Topinka, Martin, Chang, Hsiang-Kuang, Liu, Tsung-Che, Lin, Chih-Hsun, Hu, Chin-Ping, and Tsao, Che-Chih
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Astrophysics - Instrumentation and Methods for Astrophysics ,Physics - Instrumentation and Detectors - Abstract
It is well known that silicon photomultipliers (SiPMs) are prone to radiation damage. With the increasing popularity of SiPMs among new spaceborne missions, especially on CubeSats, it is of paramount importance to characterize their performance in space environment. In this work, we report the in-orbit ageing of SiPM arrays, so-called multi-pixel photon counters (MPPCs), using measurements acquired by the GRBAlpha and VZLUSAT-2 CubeSats at low Earth orbit (LEO) spanning over three years, which in duration is unique. GRBAlpha is a 1U CubeSat launched on March 22, 2021, to a 550 km altitude sun-synchronous polar orbit (SSO) carrying on board a gamma-ray detector based on CsI(Tl) scintillator readout by eight MPPCs and regularly detecting gamma-ray transients such as gamma-ray bursts and solar flares in the energy range of ~30-900 keV. VZLUSAT-2 is a 3U CubeSat launched on January 13, 2022 also to a 550 km altitude SSO carrying on board, among other payloads, two gamma-ray detectors similar to the one on GRBAlpha. We have flight-proven the Hamamatsu MPPCs S13360-3050 PE and demonstrated that MPPCs, shielded by 2.5 mm of PbSb alloy, can be used in an LEO environment on a scientific mission lasting beyond three years. This manifests the potential of MPPCs being employed in future satellites., Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section A, 13 pages, 14 figures
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- 2024
18. The Local Ultraviolet to Infrared Treasury I. Survey Overview of the Broadband Imaging
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Gilbert, Karoline M., Choi, Yumi, Boyer, Martha L., Williams, Benjamin F., Weisz, Daniel R., Bell, Eric F., Dalcanton, Julianne J., McQuinn, Kristen B. W., Skillman, Evan D., Costa, Guglielmo, Fouesneau, Morgan, Girardi, Léo, Goldman, Steven R., Gordon, Karl D., Guhathakurta, Puragra, Gull, Maude, Hagen, Lea, Huynh, Ky, Lindberg, Christina W., Marigo, Paola, Murray, Claire E., Pastorelli, Giada, and Merica-Jones, Petia Yanchulova
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Astrophysics - Astrophysics of Galaxies - Abstract
The Local Ultraviolet to Infrared Treasury (LUVIT) is a Hubble Space Telescope program that combines newly acquired data in the near ultraviolet (NUV), optical, and near infrared (NIR) with archival optical and NIR imaging to produce multiband panchromatic resolved stellar catalogs for 23 pointings in 22 low-mass, star-forming galaxies ranging in distance from the outskirts of the Local Group to ~3.8 Mpc. We describe the survey design, detail the LUVIT broadband filter observations and the archival datasets included in the LUVIT reductions, and summarize the simultaneous multiband data reduction steps. The spatial distributions and color-magnitude diagrams (CMDs) from the resulting stellar catalogs are presented for each target, from the NUV to the NIR. We demonstrate in which regions of the CMDs stars with NUV and optical, optical and NIR, and NUV through NIR detections reside. For each target, we use the results from artificial star tests to measure representative completeness, bias, and total photometric uncertainty as a function of magnitude in each broadband filter. We also assess which LUVIT targets have significant spatial variation in the fraction of stars recovered at a given magnitude. The panchromatic LUVIT stellar catalogs will provide a rich legacy dataset for a host of resolved stellar population studies., Comment: 48 pages, 14 figures, 8 tables, accepted for publication in ApJS
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- 2024
19. Run-and-tumble exact work statistics in a lazy quantum measurement engine: stochastic information processing
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Bresque, Léa, Das, Debraj, and Roldán, Édgar
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Quantum Physics ,Condensed Matter - Statistical Mechanics - Abstract
We introduce a single-qubit quantum measurement engine fuelled by backaction energy input. To reduce energetic costs associated with information processing, the measurement outcomes are only used with a prescribed laziness probability in the feedback step. As a result, we show that the work extracted over consecutive cycles is a second-order Markov process, analogous to a run-and-tumble process with transient anomalous diffusion. We derive exact analytical expressions for the work finite-time moments and first-passage-time statistics. Furthermore, we find the optimal laziness probability maximizing the mean power extracted per cycle., Comment: Supplementary Material included
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- 2024
20. A Gapless Phase with Haagerup Symmetry
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Bottini, Lea E. and Schafer-Nameki, Sakura
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High Energy Physics - Theory ,Condensed Matter - Strongly Correlated Electrons ,Mathematical Physics ,Mathematics - Category Theory ,Mathematics - Quantum Algebra - Abstract
We construct a (1+1)d gapless theory which has Haagerup $\mathcal{H}_3$ symmetry. The construction relies on the recent exploration of the categorical Landau paradigm applied to fusion category symmetries. First, using the Symmetry Topological Field Theory, we construct all gapped phases with Haagerup symmetry. Extending this construction to gapless phases, we study the second order phase transition between gapped phases, and determine analytically an Haagerup-symmetric conformal field theory. This is given in terms of two copies of the three-state Potts model, on which we realise the full $\mathcal{H}_3$ symmetry action and determine the relevant deformations to the $\mathcal{H}_3$-symmetric gapped phases. This continuum analysis is corroborated by a lattice model construction of the gapped and gapless phases, using the anyon chain., Comment: 11 pages + appendices, 2 figures
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- 2024
21. Characterizing conical intersections of nucleobases on quantum computers
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Wang, Yuchen, Cianci, Cameron, Avdic, Irma, Dutta, Rishab, Warren, Samuel, Allen, Brandon, Vu, Nam P., Santos, Lea F., Batista, Victor S., and Mazziotti, David A.
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Quantum Physics ,Physics - Chemical Physics ,Physics - Computational Physics - Abstract
Hybrid quantum-classical computing algorithms offer significant potential for accelerating the calculation of the electronic structure of strongly correlated molecules. In this work, we present the first quantum simulation of conical intersections (CIs) in a biomolecule, cytosine, using a superconducting quantum computer. We apply the Contracted Quantum Eigensolver (CQE) -- with comparisons to conventional Variational Quantum Deflation (VQD) -- to compute the near-degenerate ground and excited states associated with the conical intersection, a key feature governing the photostability of DNA and RNA. The CQE is based on an exact ansatz for many-electron molecules in the absence of noise -- a critically important property for resolving strongly correlated states at CIs. Both methods demonstrate promising accuracy when compared with exact diagonalization, even on noisy intermediate-scale quantum computers, highlighting their potential for advancing the understanding of photochemical and photobiological processes. The ability to simulate these intersections is critical for advancing our knowledge of biological processes like DNA repair and mutation, with potential implications for molecular biology and medical research.
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- 2024
22. Evolution of the radial ISM metallicity gradient in the Milky Way disk since redshift $\approx 3$
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Ratcliffe, Bridget, Khoperskov, Sergey, Minchev, Ivan, Lee, Nathan D., Buck, Tobias, Marques, Léa, Lu, Lucy, and Steinmetz, Matthias
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Astrophysics - Astrophysics of Galaxies - Abstract
Recent works identified a way to recover the time evolution of a galaxy's disk metallicity gradient from the shape of its age--metallicity relation. However, the success of the method is dependent on how the width of the star-forming region evolves over time, which in turn is dependent on a galaxy's present-day bar strength. In this paper, we account for the time variation in the width of the star-forming region when deriving the interstellar medium (ISM) metallicity gradient evolution over time ($\rm \nabla [Fe/H](\tau)$), which provides more realistic birth radii estimates of Milky Way (MW) disk stars. Using MW/Andromeda analogues from the TNG50 simulation, we quantified the disk growth of newly born stars as a function of present-day bar strength to provide a correction that improves recovery of $\rm \nabla [Fe/H](\tau)$. In TNG50, we find that our correction reduces the median absolute error in recovering $\rm \nabla [Fe/H] (\tau)$ by over 30%. To confirm its universality, we test our correction on two galaxies from NIHAO-UHD and find the median absolute error is over 3 times smaller even in the presence of observational uncertainties for the barred, MW-like galaxy. Applying our correction to APOGEE DR17 red giant MW disk stars suggests the effects of merger events on $\rm \nabla [Fe/H](\tau)$ are less significant than originally found, and the corresponding estimated birth radii expose epochs when different migration mechanisms dominated. Our correction to account for the growth of the star-forming region in the disk allows for better recovery of the evolution of the MW disk's ISM metallicity gradient and, thus, more meaningful stellar birth radii estimates. With our results, we are able to suggest the evolution of not only the ISM gradient, but also the total stellar disk radial metallicity gradient, providing key constraints to select MW analogues across redshift., Comment: submitted to A&A
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- 2024
23. Enhancement of Spontaneous Orientation Polarization in Organic Semiconductor Mixtures
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Hofmann, Alexander, Cakaj, Albin, Kolb, Lea, Noguchi, Yutaka, and Brütting, Wolfgang
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Condensed Matter - Materials Science ,Physics - Applied Physics - Abstract
The alignment of permanent dipole moments and the resulting spontaneous orientation polarization (SOP) is commonly observed in evaporated neat films of polar organic molecules and leads to a so-called giant surface potential. In case of mixed films, often enhanced molecular orientation is observed, i.e.\ a higher degree of alignment, in comparison to neat layers, if it is diluted into a suitable (non-polar) host. So far, different possible influences on molecular orientation have been discussed, the most prominent probably being the so-called surface equilibration model. In this contribution, we discuss how surface equilibration can influence orientation in mixed layers, and which other intermolecular interactions have to be considered to explain the observed enhancement of SOP in mixed layers., Comment: 12 pages, 6 figures
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- 2024
24. WHoW: A Cross-domain Approach for Analysing Conversation Moderation
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Chen, Ming-Bin, Frermann, Lea, and Lau, Jey Han
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Computer Science - Computation and Language ,I.2.7 - Abstract
We propose WHoW, an evaluation framework for analyzing the facilitation strategies of moderators across different domains/scenarios by examining their motives (Why), dialogue acts (How) and target speaker (Who). Using this framework, we annotated 5,657 moderation sentences with human judges and 15,494 sentences with GPT-4o from two domains: TV debates and radio panel discussions. Comparative analysis demonstrates the framework's cross-domain generalisability and reveals distinct moderation strategies: debate moderators emphasise coordination and facilitate interaction through questions and instructions, while panel discussion moderators prioritize information provision and actively participate in discussions. Our analytical framework works for different moderation scenarios, enhances our understanding of moderation behaviour through automatic large-scale analysis, and facilitates the development of moderator agents., Comment: 36 pages(including appendix, 10 pages main text), 8 figures, 16 tables
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- 2024
25. Truncated multiplication and batch software SIMD AVX512 implementation for faster Montgomery multiplications and modular exponentiation
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Didier, Laurent-Stéphane, Mrabet, Nadia, Glandus, Léa, and Robert, Jean-Marc
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Computer Science - Distributed, Parallel, and Cluster Computing - Abstract
This paper presents software implementations of batch computations, dealing with multi-precision integer operations. In this work, we use the Single Instruction Multiple Data (SIMD) AVX512 instruction set of the x86-64 processors, in particular the vectorized fused multiplier-adder VPMADD52. We focus on batch multiplications, squarings, modular multiplications, modular squarings and constant time modular exponentiations of 8 values using a word-slicing storage. We explore the use of Schoolbook and Karatsuba approaches with operands up to 4108 and 4154 bits respectively. We also introduce a truncated multiplication that speeds up the computation of the Montgomery modular reduction in the context of software implementation. Our Truncated Montgomery modular multiplication improvement offers speed gains of almost 20 % over the conventional non-truncated versions. Compared to the state-of-the-art GMP and OpenSSL libraries, our speedup modular operations are more than 4 times faster. Compared to OpenSSL BN_mod_exp_mont_consttimex2 using AVX512 and madd52* (madd52hi or madd52lo) in 256-bit registers, in fixed-window exponentiations of sizes 1024 and 2048 , our 512-bit implementation provides speedups of respectively 1.75 and 1.38, while the 256-bit version speedups are 1.51 and 1.05 for 1024 and 2048 -bit sizes (batch of 4 values in this case).
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- 2024
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26. Sputter Yields of the Lunar Surface: Experimental Validation and Numerical Modelling of Solar Wind Sputtering of Apollo 16 Soils
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Brötzner, Johannes, Biber, Herbert, Szabo, Paul Stefan, Jäggi, Noah, Fuchs, Lea, Nenning, Andreas, Fellinger, Martina, Nagy, Gyula, Pitthan, Eduardo, Primetzhofer, Daniel, Mutzke, Andreas, Wilhelm, Richard Arthur, Wurz, Peter, Galli, André, and Aumayr, Friedrich
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Solar and Stellar Astrophysics ,Physics - Space Physics - Abstract
Sputtering by solar wind ions is a key process driving the ejection of high-energy particles into the exospheres of airless bodies like asteroids, Mercury and the Moon. In view of upcoming missions which will deliver new in-situ data on these exospheres like the Artemis program at the Moon and BepiColombo at Mercury, a deeper understanding of sputtering effects is crucial. In this work, we combine sensitive quartz crystal microbalance measurements and numerical simulations to quantify sputter yields of Apollo soil 68501 under solar wind relevant conditions. We find that none of the commonly used simulation codes can reliably predict laboratory sputter yields without experimental benchmarks. All of the employed packages significantly overestimate the sputter yields of flat samples by at least a factor of 2 for the case of hydrogen. When accounting for surface roughness and regolith-like porosity, sputter yields are decreased even further to 7.3E-3 atoms\ion and 7.6E-2 atoms\ion for H and He at solar wind energies of 1 keV\amu, respectively. The reduced yields of porous regolith structures are largely independent of the ion incidence angle, making them applicable across a wide range of lunar latitudes. This study highlights the need for experimental validation of sputtering models to ensure accurate predictions for space weathering and lunar exosphere composition.
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- 2024
27. Signal partitioning in superfluid ${}^4$He: a Monte Carlo approach
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Toschi, Francesco, Brunold, Axel, Burmeister, Lea, Eitel, Klaus, Enss, Christian, Fascione, Eleanor, Ferber, Torben, Gabriel, Rahel, Hauswald, Lena, Kahlhoefer, Felix, Kempf, Sebastian, Klute, Markus, von Krosigk, Belina, Lindemann, Sebastian, Maier, Benedikt, Schumann, Marc, Solmaz, Melih, Valerius, Kathrin, and Wagner, Friedrich Carl
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High Energy Physics - Experiment - Abstract
Superfluid ${}^4$He is an ideal candidate for the direct detection of light dark matter via nuclear recoils thanks to its low nuclear mass and the possibility to reach a low detection energy threshold by exploiting the generated quasiparticles. The design of future detectors based on this target, such as the DELight experiment, requires a proper understanding of the formation and partitioning of the signal for different energy depositions from various sources. This work presents an overview of the physical processes involved in the energy deposition of recoiling electrons and ions, and describes a Monte Carlo approach to the partitioning of the signal into different channels. Despite an overall good agreement with existing literature, differences in the region of interest for light dark matter searches below 200\,eV are observed., Comment: 14 pages, 16 figures, 1 table
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- 2024
28. Inner ear morphology in wild versus laboratory house mice
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Renaud, Sabrina, Amar, Léa, Chevret, Pascale, Romestaing, Caroline, Quéré, Jean-Pierre, Régis, Corinne, and Lebrun, Renaud
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Quantitative Biology - Populations and Evolution - Abstract
The semicircular canals of the inner ear are involved in balance and velocity control. Being crucial to ensure efficient mobility, their morphology exhibits an evolutionary conservatism attributed to stabilizing selection. Release of selection in slow-moving animals has been argued to lead to morphological divergence and increased inter-individual variation. In its natural habitat, the house mouse Mus musculus moves in a tridimensional space where efficient balance is required. In contrast, laboratory mice in standard cages are severely restricted in their ability to move, which possibly reduces selection on the inner ear morphology. This effect was tested by comparing four groups of mice: several populations of wild mice trapped in commensal habitats in France; their second-generation laboratory offspring, to assess plastic effects related to breeding conditions; a standard laboratory strain (Swiss) that evolved for many generations in a regime of mobility reduction; and hybrids between wild offspring and Swiss mice. The morphology of the semicircular canals was quantified using a set of 3D landmarks and semi-landmarks analyzed using geometric morphometric protocols. Levels of inter-population, inter-individual (disparity) and intra-individual (asymmetry) variation were compared. All wild mice shared a similar inner ear morphology, in contrast to the important divergence of the Swiss strain. The release of selection in the laboratory strain obviously allowed for an important and rapid drift in the otherwise conserved structure. Shared traits between the inner ear of the lab strain and domestic pigs suggested a common response to mobility reduction in captivity. The lab-bred offspring of wild mice also differed from their wild relatives, suggesting plastic response related to maternal locomotory behavior, since inner ear morphology matures before birth in mammals. The signature observed in lab-bred wild mice and the lab strain was however not congruent, suggesting that plasticity did not participate to the divergence of the laboratory strain. However, contrary to the expectation, wild mice displayed slightly higher levels of inter-individual variation than laboratory mice, possibly due to the higher levels of genetic variance within and among wild populations compared to the lab strain. Differences in fluctuating asymmetry levels were detected, with the laboratory strain occasionally displaying higher asymmetry scores than its wild relatives. This suggests that there may indeed be a release of selection and/or a decrease in developmental stability in the laboratory strain., Comment: Data available as Supplementary files and a contribution in MorphoMuseuM
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- 2024
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29. Synthetic Augmentation for Anatomical Landmark Localization using DDPMs
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Hadzic, Arnela, Bogensperger, Lea, Joham, Simon Johannes, and Urschler, Martin
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Computer Science - Computer Vision and Pattern Recognition - Abstract
Deep learning techniques for anatomical landmark localization (ALL) have shown great success, but their reliance on large annotated datasets remains a problem due to the tedious and costly nature of medical data acquisition and annotation. While traditional data augmentation, variational autoencoders (VAEs), and generative adversarial networks (GANs) have already been used to synthetically expand medical datasets, diffusion-based generative models have recently started to gain attention for their ability to generate high-quality synthetic images. In this study, we explore the use of denoising diffusion probabilistic models (DDPMs) for generating medical images and their corresponding heatmaps of landmarks to enhance the training of a supervised deep learning model for ALL. Our novel approach involves a DDPM with a 2-channel input, incorporating both the original medical image and its heatmap of annotated landmarks. We also propose a novel way to assess the quality of the generated images using a Markov Random Field (MRF) model for landmark matching and a Statistical Shape Model (SSM) to check landmark plausibility, before we evaluate the DDPM-augmented dataset in the context of an ALL task involving hand X-Rays., Comment: Accepted for the SASHIMI workshop of MICCAI 2024
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- 2024
- Full Text
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30. On a Divergence Penalized Landau-de Gennes Model
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Bronsard, Lia, Chen, Jinqi, Mazzouza, Léa, McDonald, Daniel, Singh, Nathan, Stantejsky, Dominik, and van Brussel, Lee
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Mathematics - Analysis of PDEs ,Mathematics - Classical Analysis and ODEs ,35C15, 35E05, 35J50, 49S05, 76A15 - Abstract
We give a brief introduction to a divergence penalized Landau-de Gennes functional as a toy model for the study of nematic liquid crystal with colloid inclusion, in the case of unequal elastic constants. We assume that the nematic occupies the exterior of the unit ball, satisfies homeotropic anchoring at the surface of the colloid and approaches a uniform uniaxial state as $|x|\to\infty$. We study the "small particle" limit and obtain a representation formula for solutions to the associated Euler-Lagrange equations. We also present a numerical analysis of these equations based on a finite element approach and discuss the effect of the divergence penalization on the "Saturn ring" defects and on the properties of the $Q$-tensor., Comment: 15 pages, 4 figures. To be submitted to SeMA. It is based on a project as part of the Fields Undergraduate Summer Research Program
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- 2024
31. Estimating Body and Hand Motion in an Ego-sensed World
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Yi, Brent, Ye, Vickie, Zheng, Maya, Müller, Lea, Pavlakos, Georgios, Ma, Yi, Malik, Jitendra, and Kanazawa, Angjoo
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Artificial Intelligence - Abstract
We present EgoAllo, a system for human motion estimation from a head-mounted device. Using only egocentric SLAM poses and images, EgoAllo guides sampling from a conditional diffusion model to estimate 3D body pose, height, and hand parameters that capture the wearer's actions in the allocentric coordinate frame of the scene. To achieve this, our key insight is in representation: we propose spatial and temporal invariance criteria for improving model performance, from which we derive a head motion conditioning parameterization that improves estimation by up to 18%. We also show how the bodies estimated by our system can improve the hands: the resulting kinematic and temporal constraints result in over 40% lower hand estimation errors compared to noisy monocular estimates. Project page: https://egoallo.github.io/, Comment: v2: fixed figures for Safari, typos
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- 2024
32. Fake It Until You Break It: On the Adversarial Robustness of AI-generated Image Detectors
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Mavali, Sina, Ricker, Jonas, Pape, David, Sharma, Yash, Fischer, Asja, and Schönherr, Lea
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
While generative AI (GenAI) offers countless possibilities for creative and productive tasks, artificially generated media can be misused for fraud, manipulation, scams, misinformation campaigns, and more. To mitigate the risks associated with maliciously generated media, forensic classifiers are employed to identify AI-generated content. However, current forensic classifiers are often not evaluated in practically relevant scenarios, such as the presence of an attacker or when real-world artifacts like social media degradations affect images. In this paper, we evaluate state-of-the-art AI-generated image (AIGI) detectors under different attack scenarios. We demonstrate that forensic classifiers can be effectively attacked in realistic settings, even when the attacker does not have access to the target model and post-processing occurs after the adversarial examples are created, which is standard on social media platforms. These attacks can significantly reduce detection accuracy to the extent that the risks of relying on detectors outweigh their benefits. Finally, we propose a simple defense mechanism to make CLIP-based detectors, which are currently the best-performing detectors, robust against these attacks.
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- 2024
33. Protected Fluxonium Control with Sub-harmonic Parametric Driving
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Schirk, Johannes, Wallner, Florian, Huang, Longxiang, Tsitsilin, Ivan, Bruckmoser, Niklas, Koch, Leon, Bunch, David, Glaser, Niklas J., Huber, Gerhard B. P., Knudsen, Martin, Krylov, Gleb, Marx, Achim, Pfeiffer, Frederik, Richard, Lea, Roy, Federico A., Romeiro, João H., Singh, Malay, Södergren, Lasse, Dionis, Etienne, Sugny, Dominique, Werninghaus, Max, Liegener, Klaus, Schneider, Christian M. F., and Filipp, Stefan
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Quantum Physics - Abstract
Protecting qubits from environmental noise while maintaining strong coupling for fast high-fidelity control is a central challenge for quantum information processing. Here, we demonstrate a novel control scheme for superconducting fluxonium qubits that eliminates qubit decay through the control channel by reducing the environmental density of states at the transition frequency. Adding a low-pass filter on the flux line allows for flux-biasing and at the same time coherently controlling the fluxonium qubit by parametrically driving it at integer fractions of its transition frequency. We compare the filtered to the unfiltered configuration and find a five times longer $T_1$, and ten times improved $T_2$-echo time in the protected case. We demonstrate coherent control with up to 11-photon sub-harmonic drives, highlighting the strong non-linearity of the fluxonium potential. We experimentally determine Rabi frequencies and drive-induced frequency shifts in excellent agreement with numerical and analytical calculations. Furthermore, we show the equivalence of a 3-photon sub-harmonic drive to an on-resonance drive by benchmarking sub-harmonic gate fidelities above 99.94 %. These results open up a scalable path for full qubit control via a single protected channel, strongly suppressing qubit decoherence caused by control lines., Comment: 18 pages, 9 figures
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- 2024
34. Gambling Carnot Engine
- Author
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Tohme, Tarek, Bedoya, Valentina, di Bello, Costantino, Bresque, Léa, Manzano, Gonzalo, and Roldán, Édgar
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Condensed Matter - Statistical Mechanics ,Condensed Matter - Soft Condensed Matter - Abstract
We propose a theoretical model for a colloidal heat engine driven by a feedback protocol that is able to fully convert the net heat absorbed by the hot bath into extracted work. The feedback protocol, inspired by gambling strategies, executes a sudden quench at zero work cost when the particle position satisfies a specific first-passage condition. As a result, the engine enhances both power and efficiency with respect to a standard Carnot cycle, surpassing Carnot's efficiency at maximum power. Using first-passage and martingale theory, we derive analytical expressions for the power and efficiency far beyond the quasistatic limit and provide scaling arguments for their dependency with the cycle duration. Numerical simulations are in perfect agreement with our theoretical findings, and illustrate the impact of the data acquisition rate on the engine's performance., Comment: 20 pages (including supplemental material), 8 figures (including supplemental figures)
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- 2024
35. AI-driven View Guidance System in Intra-cardiac Echocardiography Imaging
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Huh, Jaeyoung, Klein, Paul, Funka-Lea, Gareth, Sharma, Puneet, Kapoor, Ankur, and Kim, Young-Ho
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Computer Science - Artificial Intelligence - Abstract
Intra-cardiac Echocardiography (ICE) is a crucial imaging modality used in electrophysiology (EP) and structural heart disease (SHD) interventions, providing real-time, high-resolution views from within the heart. Despite its advantages, effective manipulation of the ICE catheter requires significant expertise, which can lead to inconsistent outcomes, particularly among less experienced operators. To address this challenge, we propose an AI-driven closed-loop view guidance system with human-in-the-loop feedback, designed to assist users in navigating ICE imaging without requiring specialized knowledge. Our method models the relative position and orientation vectors between arbitrary views and clinically defined ICE views in a spatial coordinate system, guiding users on how to manipulate the ICE catheter to transition from the current view to the desired view over time. Operating in a closed-loop configuration, the system continuously predicts and updates the necessary catheter manipulations, ensuring seamless integration into existing clinical workflows. The effectiveness of the proposed system is demonstrated through a simulation-based evaluation, achieving an 89% success rate with the 6532 test dataset, highlighting its potential to improve the accuracy and efficiency of ICE imaging procedures.
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- 2024
36. A Roadmap for Simulating Chemical Dynamics on a Parametrically Driven Bosonic Quantum Device
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Cabral, Delmar G. A., Khazaei, Pouya, Allen, Brandon C., Videla, Pablo E., Schäfer, Max, Cortiñas, Rodrigo G., de Albornoz, Alejandro Cros Carrillo, Chávez-Carlos, Jorge, Santos, Lea F., Geva, Eitan, and Batista, Victor S.
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Quantum Physics ,Physics - Chemical Physics - Abstract
Chemical reactions are commonly described by the reactive flux transferring population from reactants to products across a double-well free energy barrier. Dynamics often involves barrier recrossing and quantum effects like tunneling, zero-point energy motion and interference, which traditional rate theories, such as transition-state theory, do not consider. In this study, we investigate the feasibility of simulating reaction dynamics using a parametrically driven bosonic superconducting Kerr-cat device. This approach provides control over parameters defining the double-well free energy profile, as well as external factors like temperature and the coupling strength between the reaction coordinate and the thermal bath of non-reactive degrees of freedom. We demonstrate the effectiveness of this protocol by showing that the dynamics of proton transfer reactions in prototypical benchmark model systems, such as hydrogen bonded dimers of malonaldehyde and DNA base pairs, could be accurately simulated on currently accessible Kerr-cat devices.
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- 2024
37. orbitize! v3: Orbit fitting for the High-contrast Imaging Community
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Blunt, Sarah, Wang, Jason Jinfei, Hirsch, Lea, Tejada, Roberto, Nagpal, Vighnesh, Surti, Tirth Dharmesh, Covarrubias, Sofia, McKenna, Thea, Chávez, Rodrigo Ferrer, Llop-Sayson, Jorge, Arora, Mireya, Chavez, Amanda, Cody, Devin, Choudhary, Saanika, Smith, Adam J. R. W., Balmer, William, Stolker, Tomas, Gallamore, Hannah, Ó, Clarissa R. Do, Nielsen, Eric L., and De Rosa, Robert J.
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
orbitize! is a package for Bayesian modeling of the orbital parameters of resolved binary objects from time series measurements. It was developed with the needs of the high-contrast imaging community in mind, and has since also become widely used in the binary star community. A generic orbitize! use case involves translating relative astrometric time series, optionally combined with radial velocity or astrometric time series, into a set of derived orbital posteriors. This paper is published alongside the release of orbitize! version 3.0, which has seen significant enhancements in functionality and accessibility since the release of version 1.0 (Blunt et al., 2020)., Comment: Published in JOSS
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- 2024
38. Prompt Obfuscation for Large Language Models
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Pape, David, Eisenhofer, Thorsten, and Schönherr, Lea
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Computer Science - Cryptography and Security ,Computer Science - Machine Learning - Abstract
System prompts that include detailed instructions to describe the task performed by the underlying large language model (LLM) can easily transform foundation models into tools and services with minimal overhead. Because of their crucial impact on the utility, they are often considered intellectual property, similar to the code of a software product. However, extracting system prompts is easily possible by using prompt injection. As of today, there is no effective countermeasure to prevent the stealing of system prompts and all safeguarding efforts could be evaded with carefully crafted prompt injections that bypass all protection mechanisms. In this work, we propose an alternative to conventional system prompts. We introduce prompt obfuscation to prevent the extraction of the system prompt while maintaining the utility of the system itself with only little overhead. The core idea is to find a representation of the original system prompt that leads to the same functionality, while the obfuscated system prompt does not contain any information that allows conclusions to be drawn about the original system prompt. We implement an optimization-based method to find an obfuscated prompt representation while maintaining the functionality. To evaluate our approach, we investigate eight different metrics to compare the performance of a system using the original and the obfuscated system prompts, and we show that the obfuscated version is constantly on par with the original one. We further perform three different deobfuscation attacks and show that with access to the obfuscated prompt and the LLM itself, we are not able to consistently extract meaningful information. Overall, we showed that prompt obfuscation can be an effective method to protect intellectual property while maintaining the same utility as the original system prompt.
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- 2024
39. Conservation of angular momentum on a single-photon level
- Author
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Kopf, Lea, Barros, Rafael, Prabhakar, Shashi, Giese, Enno, and Fickler, Robert
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Quantum Physics - Abstract
Identifying conservation laws is central to every subfield of physics, as they illuminate the underlying symmetries and fundamental principles. These laws have far-reaching implications, not only enhancing our theoretical understanding but also enabling practical applications. A prime example can be found in quantum optics: The conservation of orbital angular momentum (OAM) during spontaneous parametric down-conversion (SPDC) enables the generation of a photon pair with entangled OAM. This quantum correlation is commonly attributed to the conservation of the topological charge of a strong coherent pump field driving the process. However, the topological charge of such a classical field only determines the average OAM per photon, so that the total OAM carried by the field has fluctuations as a direct consequence of its photon statistics. In this article, we report on the first realisation of SPDC pumped by a single twisted photon. Our results confirm OAM conservation at the single-photon level and directly transfer to SPDC induced by classical pump fields by averaging over their photon statistics. In addition to verifying a central property of SPDC, our results present the first implementation of cascaded down-conversion in bulk media, setting the stage for experiments on the direct generation of multi-photon high-dimensional entanglement using all degrees of freedom of light.
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- 2024
40. Coma composition and profiles of comet 12P/Pons-Brooks using long-slit spectroscopy
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Ferellec, Lea, Opitom, Cyrielle, Donaldson, Abbie, Fynbo, Johan P. U., Kokotanekova, Rosita, Kelley, Michael S. P., and Lister, Tim
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Astrophysics - Earth and Planetary Astrophysics - Abstract
Comet 12P/Pons-Brook exhibited multiple large and minor outbursts in 2023 on its way to its 2024 perihelion, as it has done during its previous apparitions. We obtained long-slit optical spectra of the comet in 2023 August and 2023 November with the INT-IDS, and in 2023 December with NOT-ALFOSC. Using a standard Haser model in a 10000km-radius aperture and commonly used empirical parent and daughter scale-lengths, our calculated abundance ratios show a constant "typical" composition throughout the period with a C$_2$/CN ratio of about 90 per cent. Molecular density profiles of different species along the slit show asymmetries between opposite sides of the coma and that C$_2$ seems to behave differently than CN and C$_3$. Comparing the coma profiles to a standard Haser model shows that this model cannot accurately reproduce the shape of the coma, and therefore that the calculated production rates cannot be deemed as accurate. We show that an outburst Haser model is a {slightly} better match to the C$_3$ and CN profile shapes, but the model still does not explain the shape of the C$_2$ profiles and requires equal parent and daughter scale-lengths. Our results suggest that the coma morphology could be better explained by extended sources, and that the nature of 12P's activity introduces bias in the determination of its composition., Comment: 11 pages, 7 figures, accepted for publication in MNRAS
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- 2024
- Full Text
- View/download PDF
41. Fast Projected Bispectra: the filter-square approach
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Harscouet, Lea, Cowell, Jessica A., Ereza, Julia, Alonso, David, Camacho, Hugo, Nicola, Andrina, and Slosar, Anze
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The study of third-order statistics in large-scale structure analyses has been hampered by the increased complexity of bispectrum estimators (compared to power spectra), the large dimensionality of the data vector, and the difficulty in estimating its covariance matrix. In this paper we present the filtered-squared bispectrum (FSB), an estimator of the projected bispectrum effectively consisting of the cross-correlation between the square of a field filtered on a range of scales and the original field. Within this formalism, we are able to recycle much of the infrastructure built around power spectrum measurement to construct an estimator that is both fast and robust against mode-coupling effects caused by incomplete sky observations. Furthermore, we demonstrate that the existing techniques for the estimation of analytical power spectrum covariances can be used within this formalism to calculate the bispectrum covariance at very high accuracy, naturally accounting for the most relevant Gaussian and non-Gaussian contributions in a model-independent manner., Comment: 34 pages, 13 figures
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- 2024
42. Core Revelations: the Star Formation and AGN Connection at the Heart of NGC 7469
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Feuillet, Léa M., Kraemer, Steve, Meléndez, Marcio B., Fischer, Travis C., Schmitt, Henrique R., Reeves, James N., and Falcão, Anna Trindade
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Astrophysics - Astrophysics of Galaxies - Abstract
We investigate the star formation-AGN connection in the Seyfert 1 NGC 7469 using James Webb Space Telescope (JWST) mid-infrared spectroscopic integral field unit (IFU) data. We use the IFU data to generate maps of different emission lines present in the spectrum, such as the star-formation (SF) tracer [Ne II] 12.81{\mu}m, or the AGN tracer [Ne V] 14.32{\mu}m. We can separate the AGN- and SF-dominated regions using spatially resolved mid-IR diagnostic diagrams, and further investigate the ionization sources powering each region by constructing photoionization models. We find that the previously detected eastern wind populates an intermediary region of the diagrams, between our star-forming and AGN quadrants. This wind also coincides with a reduction in the [Ne II] emission in the ring, which suggests that the ionization cone intersects the ring in this direction. In spite of this evidence of negative AGN feedback, given the narrow opening angle of the ionization cone and its orientation, this would not be a case of efficient feedback., Comment: 13 pages, 6 figures, submitted to ApJ
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- 2024
43. HexaCoder: Secure Code Generation via Oracle-Guided Synthetic Training Data
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Hajipour, Hossein, Schönherr, Lea, Holz, Thorsten, and Fritz, Mario
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Computer Science - Cryptography and Security ,Computer Science - Artificial Intelligence ,Computer Science - Computation and Language ,Computer Science - Machine Learning ,Computer Science - Software Engineering - Abstract
Large language models (LLMs) have shown great potential for automatic code generation and form the basis for various tools such as GitHub Copilot. However, recent studies highlight that many LLM-generated code contains serious security vulnerabilities. While previous work tries to address this by training models that generate secure code, these attempts remain constrained by limited access to training data and labor-intensive data preparation. In this paper, we introduce HexaCoder, a novel approach to enhance the ability of LLMs to generate secure codes by automatically synthesizing secure codes, which reduces the effort of finding suitable training data. HexaCoder comprises two key components: an oracle-guided data synthesis pipeline and a two-step process for secure code generation. The data synthesis pipeline generates pairs of vulnerable and fixed codes for specific Common Weakness Enumeration (CWE) types by utilizing a state-of-the-art LLM for repairing vulnerable code. A security oracle identifies vulnerabilities, and a state-of-the-art LLM repairs them by extending and/or editing the codes, creating data pairs for fine-tuning using the Low-Rank Adaptation (LoRA) method. Each example of our fine-tuning dataset includes the necessary security-related libraries and code that form the basis of our novel two-step generation approach. This allows the model to integrate security-relevant libraries before generating the main code, significantly reducing the number of generated vulnerable codes by up to 85% compared to the baseline methods. We perform extensive evaluations on three different benchmarks for four LLMs, demonstrating that HexaCoder not only improves the security of the generated code but also maintains a high level of functional correctness., Comment: 24 pages, 16 tables, 8 figures
- Published
- 2024
44. Synergy and Synchrony in Couple Dances
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Maluleke, Vongani, Müller, Lea, Rajasegaran, Jathushan, Pavlakos, Georgios, Ginosar, Shiry, Kanazawa, Angjoo, and Malik, Jitendra
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Computer Science - Computer Vision and Pattern Recognition - Abstract
This paper asks to what extent social interaction influences one's behavior. We study this in the setting of two dancers dancing as a couple. We first consider a baseline in which we predict a dancer's future moves conditioned only on their past motion without regard to their partner. We then investigate the advantage of taking social information into account by conditioning also on the motion of their dancing partner. We focus our analysis on Swing, a dance genre with tight physical coupling for which we present an in-the-wild video dataset. We demonstrate that single-person future motion prediction in this context is challenging. Instead, we observe that prediction greatly benefits from considering the interaction partners' behavior, resulting in surprisingly compelling couple dance synthesis results (see supp. video). Our contributions are a demonstration of the advantages of socially conditioned future motion prediction and an in-the-wild, couple dance video dataset to enable future research in this direction. Video results are available on the project website: https://von31.github.io/synNsync
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- 2024
45. Physically constrained quantum clock-driven dynamics
- Author
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Cilluffo, Dario, Lautenbacher, Lea, Spaventa, Giovanni, Huelga, Susana F., and Plenio, Martin B.
- Subjects
Quantum Physics - Abstract
Thermal machines are physical systems specifically designed to make thermal energy available for practical use through state transformations in a cyclic process. This concept relies on the presence of an additional element equipped with a clock, controlling which interaction Hamiltonian between the system and the reservoirs must act at a certain time and that remains unaffected during this process. In the domain of quantum dynamics, there is substantial evidence to suggest that fulfilling this final condition is, in fact, impossible, except in ideal and far-from-reality cases. In this study we start from one such idealized condition and proceed to relax the primary approximations to make the model more realistic and less ideal. The main result is a fully quantum description of the engine-clock dynamics within a realistic quantum framework. Furthermore, this approach offers the possibility to address the deeper and more fundamental challenge of defining meaningful time operators in the realm of quantum mechanics from a different standpoint., Comment: 9 pages, 2 figures
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- 2024
46. The Multilayered Effects of Racism on Early Educators in California: An Examination of Disparities in Wages, Leadership Roles, and Education
- Author
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University of California, Berkeley. Center for the Study of Child Care Employment, Yoonjeon Kim, Lea J. E. Austin, and Hopeton Hess
- Abstract
Despite the crucial role early educators play in young children's development, the field has always struggled with poor compensation and inadequate support (McLean et al., 2021). The persistent undervaluation of the ECE sector and the labor provided by the nearly all-female workforce can be traced back to its racist roots, when enslaved Black women were forced to care for White children (Center for the Study of Child Care Employment, 2022a; Lloyd et al., 2021). This report shows how racism continues to affect the ECE workforce. Racial disparities take many forms, from inequities in racial and ethnic representation across provider types and job roles to disparities in compensation. Black and Latina educators, for example, routinely experience lower wages than their peers. Asian and Black educators tend to hold higher levels of educational degrees compared to other groups, but their credentials do not necessarily lead to job advancement or higher pay. Systemic racism is most often understood as a form of racism that is "pervasively and deeply embedded in systems, laws, written or unwritten policies, and entrenched practices and beliefs that produce, condone, and perpetuate widespread unfair treatment and oppression of people of color" (Braveman et al., 2022, p. 171). Yet, systemic racism also fosters an absence of systems or processes that provide recourse for discrimination or protection from inequities. A transformed system could begin to repair the current injustices. (1) For example, if early care and education were treated as a public good, programs would be funded to reflect the true cost of care; (2) A salary scale driven by a combination of years of experience and education would reduce the vast pay gaps, especially between Black educators and their peers of other races and ethnicities with similar education and experience; (3) Professional pathway programs and mentorship initiatives could be designed specifically to expand access to leadership roles for underrepresented communities. Efforts like apprenticeships, degree-completion programs, and fellowships have proven incredibly successful (Copeman Petig et al., 2019; Kipnis et al., 2012; Smith et al., 2023). However, such opportunities are not built into ECE systems, but are often pilots, demonstration projects, or very limited in reach (Malone et al., 2021); and (3) Data to pinpoint disparities could track how or if they are reduced over time. North Carolina, for example, routinely funds robust data collection, but it is unclear if and how identified disparities are acted on (Child Care Services Association, 2020). [Additional funding for this report was provided by the Blue Shield of California Foundation.]
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- 2024
47. The Early Care and Education Workforce of Contra Costa County
- Author
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University of California, Berkeley. Center for the Study of Child Care Employment (CSCCE), Anna Powell, Wanzi Muruvi, Lea J. E. Austin, and Abby Copeman Petig
- Abstract
Early care and education (ECE) programs are central to a thriving community: they support the well-being of children as well as their families. In Contra Costa County, approximately 260 child care centers serve children from birth through age five, along with 765 family child care providers operating in their own homes. These nurturing and vibrant learning environments reflect the ECE workforce, a highly skilled yet undervalued professional group of nearly 4,000 individuals. Building on the "California Early Care and Education Workforce Study," this report provides a snapshot of the state of the licensed ECE workforce in Contra Costa County. Chapter 1 offers a profile of its core members: family child care providers and center-based educators (directors, teachers, and assistants). Chapter 2 describes the state of educator well-being, and Chapter 3 explores stability for center- and home-based programs and for professionals in the field. [This report was funded by First 5 Contra Costa, the Contra Costa County Office of Education/Local Planning Council, the Contra Costa County Employment Human Services Department's Community Services Bureau, and CoCoKids.]
- Published
- 2024
48. Effects of Racist Microaggressions and Sexual and Gender Minority Stress on Mental Health among Latinx Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning + Young Adults
- Author
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John P. Salerno, Charles H. Lea, and Carmela Alcántara
- Abstract
This study examines the effects of racist microaggressions and lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ)-related minority stressors (i.e., identity concealment, family rejection, internalized LGBTQ-phobia, victimization, and racialized heterosexism/cisgenderism) on psychological distress among Latinx LGBTQ+ young people, specifically college students. Participants are a Latinx subset (n = 80) from a national online nonprobability cross-sectional survey of LGBTQ+ college students. The study aim was examined using linear/logistic regression. Findings indicated that racist microaggressions and family rejection were associated with psychological distress. In addition, racist microaggressions were the only stressor associated with clinically significant psychological distress that may warrant psychiatric/psychological treatment. Therefore, racist microaggressions and family rejection are unique stressors that may saliently affect mental health among Latinx LGBTQ+ students. There is a great need to integrate minority stress theory with other critically-oriented theories, such as intersectionality, in research and intervention to eliminate mental health inequities faced by Latinx LGBTQ+ young people.
- Published
- 2024
- Full Text
- View/download PDF
49. The Emotional and Physical Well-Being of Early Educators in California. Early Educator Well-Being Series. Report
- Author
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University of California, Berkeley. Center for the Study of Child Care Employment, Wanzi Muruvi, Anna Powell, Yoonjeon Kim, Abby Copeman Petig, and Lea J. E. Austin
- Abstract
Working with young children is intellectually, emotionally, and physically demanding. These challenges are compounded by the inadequate compensation that characterizes the early care and education (ECE) sector and lack of workplace support such as access to health benefits, retirement plans, and time off (Montoya et al., 2022). The cumulative strain can intensify the stress experienced by early educators, adversely affecting both their emotional and physical well-being (Cumming, 2017). The California Early Care and Education Workforce Study is an ongoing longitudinal study that provides comprehensive statewide and regional information on the center- and home-based ECE workforce. The Center for the Study of Child Care Employment (CSCCE) launched the current workforce study in 2020 to provide an update on the status of the workforce since the previous study in 2006 (Whitebook et al., 2006). Phase 2 of the present study was conducted during 2023, collecting information predominantly from educators who had participated in 2020. This report focuses on the emotional and physical well-being of California's ECE workforce who work with children birth to age five. It is the first in a series on early educator well-being, highlighting findings from Phase 2 of the California Early Care and Education Workforce Study. [Also acknowledged was funding by Blue Shield of California Foundation.]
- Published
- 2023
50. Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes
- Author
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Pasquini, Lorenzo, Pereira, Felipe L, Seddighi, Sahba, Zeng, Yi, Wei, Yongbin, Illán-Gala, Ignacio, Vatsavayai, Sarat C, Friedberg, Adit, Lee, Alex J, Brown, Jesse A, Spina, Salvatore, Grinberg, Lea T, Sirkis, Daniel W, Bonham, Luke W, Yokoyama, Jennifer S, Boxer, Adam L, Kramer, Joel H, Rosen, Howard J, Humphrey, Jack, Gitler, Aaron D, Miller, Bruce L, Pollard, Katherine S, Ward, Michael E, and Seeley, William W
- Subjects
Biological Psychology ,Psychology ,Acquired Cognitive Impairment ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Genetics ,Brain Disorders ,Rare Diseases ,Alzheimer's Disease Related Dementias (ADRD) ,Frontotemporal Dementia (FTD) ,Alzheimer's Disease ,Dementia ,Aging ,Neurosciences ,2.1 Biological and endogenous factors ,Neurological ,Humans ,Frontotemporal Lobar Degeneration ,Brain ,Male ,Female ,Aged ,DNA-Binding Proteins ,Middle Aged ,tau Proteins ,Atrophy ,Animals ,Evolution ,Molecular ,Gene Expression ,frontotemporal lobar degeneration ,cryptic exon ,human accelerated regions ,TDP-43 ,tau ,gene expression ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences - Abstract
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.
- Published
- 2024
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